Steroids and neuronal destruction or stabilization.
Extensive work has indicated that glucocorticoid steroids may play a role in promoting age-related central neuronal degeneration. It has also been shown that glucocorticoid supplementation may intensify acute post-ischaemic neuronal necrosis and that prior adrenalectomy is protective. A glucocorticoid inhibition of injury-induced axonal reactive sprouting has also been reported. The mechanism of this deleterious effect on chronic or acute neuronal degeneration and regenerative responses is thought to involve specific glucocorticoid receptors either on susceptible nerve cells or on adjacent glial cells. However, other studies have shown that intensive short-term glucocorticoid treatment may attenuate post-traumatic and post-ischaemic central neuronal damage. Anterograde degeneration of motor nerve fibres can also be retarded by intensive glucocorticoid pretreatment. The mechanism of these high dose protective effects appears to involve an intrinsic ability of certain glucocorticoids to inhibit oxygen free radical-induced lipid peroxidation, a phenomenon that may be fundamentally involved in neuronal degeneration. Recently, steroid analogues which lack glucocorticoid receptor affinity have been shown to duplicate the antioxidant and cerebroprotective actions of the glucocorticoids in models of neuronal damage. Thus, the deleterious and protective effects of steroids on neuronal viability depend on two different mechanisms, separable by dose, duration of treatment, specific situation and chemical structure.
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Central Nervous System Diseases Research Unit, Upjohn Company, Kalamazoo, MI 49001.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D009410:Nerve Degeneration / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013256:Steroids / Q000494:pharmacology*
D005938:Glucocorticoids; D013256:Steroids